The “-omics” of Nutrient Metabolism

How our bodies use the nutrients that nourish us drives much of the science at the Nutrition Research Institute. Recent advances in nutrition studies have shed light on the metabolic fates of nutrients and about the molecular actors and mechanisms responsible for the underlying processes. A major reason for the explosive advances in the understanding of nutrient metabolism has been the massive investigative use of all kinds of “-omics,” new fields of study for the mining of data-rich biological information.

One of these high-resolution technologies is genomics. We now know most genes. A few may still play hard to get, but there are not going to be a lot of surprises. The attention, therefore, has turned increasingly to the multiple products individual genes can generate, how their production is regulated, and what the gene products actually do. High-throughput analyzers, which can read millions of DNA or RNA bases in days, have made it possible to study genes and their expression in detail in many different species of model animals and in human populations. Who would have thought that that the blood group secretor status is a major determinant of vitamin B12 sufficiency in older adults? A wave of genome-wide association studies has yielded this and many other new and often unexpected insights into the inner workings of nutrient metabolism.

We can also use epigenomics to monitor in detail many chemical modifications of particular DNA sequences. The best known kind will usually silence expression of the associated gene. Each cell type has its own set of characteristic epigenetic modifications that determine the nature of the cells and what they do. While many modification patterns are tissue specific, others are shared more globally and can be read from blood cells. Several nutrients are important for the epigenetic status at numerous DNA sites of interest because they are needed for a steady supply of methyl groups for DNA modification. Research in recent years has greatly increased our understanding of the relevant pathways, variation of the involved genes, and the role of nutrients, phytochemicals, and feeding status in setting epigenetic patterns.

The advances in proteomics also have had their share in deepening the understanding of nutrient metabolism. Proteomic analyses, which look at proteins and peptides from different tissues and cell lines with high-resolution techniques, have concluded that fewer than 20,000 genes are coding for proteins. The approach has helped to clarify in which tissues particular proteins are present and contribute to nutrient metabolism there.

Many of the new insights have come from metabolomic analyses. This approach measures many different small metabolites in fluids and tissues. Current technologies already can distinguish several thousand different compounds and this number is rapidly growing. The distinct compounds in foods and the metabolic products derived from them most likely are more than one hundred thousand in number. An understanding of the nature of food constituents, their properties, and typical conversions helps with the interpretation of complex chemical signatures in the body.

The role of gut bacteria is explored by microbiomics. The human intestines contain about ten times as many microorganisms as there are cells in the human body taken together. The collection of bacteria, yeasts, and viruses in the intestinal tract constitute the human gut microbiome. Many microbiota are metabolically very active. They partake of the food that comes their way, convert some of the dietary fiber into fuels for their host, and provide essential vitamins. They also chemically alter bile acids and other intestinal compounds before they are absorbed. Thus, the gut microbiome functions like a chemical factory that is normally well integrated into overall human metabolism and critically important for good health. The shifts in the balance of many nutrients due to disruption of the microbiome by dietary factors, infections, or antibiotics are increasingly recognized, opening up new approaches for prevention and treatment of diseases.

Despite our rapidly growing recognition of extensive genomic and metabolic diversity even within seemingly homogenous populations, current intake recommendations still assume that everybody has more or less the same metabolism. This is certainly contradicted by the known genomic, proteomic, metabolomic, and microbiomic variations that make each of us different, sometimes very different. The smallest structural difference in an enzyme, transporter, or receptor can profoundly change its function and alter how much of a nutrient an individual needs. Similarly, common epigenetic alterations of our genome and subtle shifts in microbiome patterns have important nutritional implications. The scientists at the Nutrition Research Institute are working to put the nutritional consequences of such functional differences into perspective.